The central aim of this proposal is to dissect the cellular and molecular responses of the lung to acute injury. These studies will rely on a variety of cutting edge microscopic methods to support other physiologic and molecular approaches to study lung injury and cytoprotection in epithelial and endothelial cells. Therefore a central histopathology and imaging core is defined as an integral component of this proposal. The Core will be housed in the Center for Biologic Imaging (CBI) of the University of Pittsburgh Medical Center. This Center is equipped to perform a continuum of optical methods including all types of microscopy essential to this Program Project. Within the scope of this Program light microscopic techniques include: conventional histological, immuno-histological, laser confocal, and in situ hybridization methods, as well as multiparametric ratiometric methods and live cell and tissue imaging technologies. Our considerable experience in computerized image processing and morphometry will allow quantitative analysis of observed phenomena to corroborate subtle qualitative changes, and this a major function of the Core in this Program. At the electron microscopic level thin section electron microscopy and immuno-electron microscopic evaluation of specimens as a natural extension of the light microscopic analyses will be employed when needed. The CBI has continued its extensive interactions with the project leaders, this is reflected in extensive changes to the preliminary data section and given the success of these interactions we expect a continued expansion in the use of optical techniques within this formal program setting.